Risk of selected gastrointestinal toxicities in metastatic renal cell carcinoma patients treated with immuno-TKI combinations: a meta-analysis.

OBJECTIVE

Recent years have registered the advent of novel treatment options for metastatic renal cell carcinoma (mRCC), including combination therapies with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Immuno-TKI combinations have been suggested to improve clinical outcomes but may also result in increased toxicity, including gastrointestinal (GI) adverse events.

METHODS

Herein, we performed a meta-analysis aimed at comparing the risk of certain GI toxicities in mRCC patients treated with immuno-TKI combinations versus sunitinib monotherapy. Overall, four phase III trials (KEYNOTE-426, JAVELIN Renal 101, CheckMate 9ER, CLEAR) involving 3059 mRCC patients were available.

RESULTS

The meta-analysis suggested an increased risk of all-grade diarrhea, grade 3-4 diarrhea and grade 3-4 decreased appetite in patients treated with immuno-TKI combinations. Conversely, an apparently higher risk of all-grade nausea was observed in the sunitinib group.

CONCLUSION

The meta-analysis suggested that immuno-TKI combinations are associated with higher risk of GI toxicities compared with sunitinib. Beyond the efficacy of immuno-TKI combinations in mRCC patients, careful consideration should be given to treatment-related adverse events, including GI toxicities. Early recognition and treatment are critical to maximize recovery.